Oral Switch During Treatment of Left-sided Endocarditis Due to Multi-susceptible Staphylococcus

Inclusion Criteria:

• Left-sided IE (Defined according to Duke criteria) on native or prosthetic valve
• due to one isolate of Staphylococcus sp. (S. aureus or coagulase negativestaphylococci, CNS) susceptible to levofloxacin and rifampicin
• in an adult ≥18 year old
• appropriate parenteral antibiotics treatment received for at least 10 days
• in case of valvular surgery, appropriate parenteral antibiotics treatment received forat least 10 days after valvular surgery
• planned duration of antibiotics will extend for at least 14 days at the time ofrandomisation i.e. a potential switch to oral treatment between Day 10 and Day 28 thusensuring to have at least 14 days of oral therapy remaining in the experimental group
• apyrexia (temperature < 38°C) at each time point during the last 48 hours (at leasttwo measures/day) at the time of randomisation
• blood cultures have been sterile for at least 5 days at the time of randomisation
• informed, written consent obtained from patient
• subject covered by or having the rights to French social security

Exclusion Criteria:

• body mass index <15 kg/m² or > 40 kg/m²
• glomerular filtration rate < 50 ml/min/1,73m²
• patient unable or unwilling to take oral treatment (digestive intolerance, significantmalabsorption) at the time of randomisation
• expected difficulties regarding compliance with oral antibiotic treatment or follow-up (e.g. severe cognitive impairment, severe psychiatric disease...)
• patient without entourage to support and watch him at discharge
• valvular surgery planned within the next 6 months
• patients with cardiac devices (pace-maker, implantable cardiac defibrillator) andsuspected device-related IE (vegetation on the leads) if removal of the device was notperformed
• breast feeding or pregnant women, or women on childbearing age without effectivecontraception
• expected duration of follow-up < 7 months at the time of randomisation (e.g. expectedlife expectancy < 7 months, patient living abroad...)
• past medical history of IE in the last 3 months
• other infection requiring parenteral antibiotic therapy
• taking of an estrogen-progesterone treatment interacting with rifampicin
• patient with contra-indication to oral antibiotics administered in the experimentalarm (i.e. fluoroquinolones or rifampicin ) - including anticipated non-manageable druginteractions with rifampicin, and allergy.